Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma that originate from peripheral nerves or from cells associated with the nerve sheath. We report the case of a 30‑year‑old male patient with a history of neurofibromatosis type I (NF-1) and a MPNST located in the lumbar region. The mass was resecated but surgical margins weren't clear. Recurrence of disease was observed after few months. A close monitoring of subjects with NF-1 is crucial to diagnose MPNST at an earlier stage and allow a complete surgical resection

Eusebi, Laura

Guglielmi, Giuseppe

Mazzucchelli, Roberta

Paparella, Maria Teresa

English

Archivio Istituzionale della Ricerca- Università degli Studi di Foggia

Acta Biomed 2022; Vol. 93, Supplement 1: e2022095 DOI 10.23750/abm.v93iS1.12360 © Mattioli 1885C a s e  r e p o r tLumbar malignant peripheral nerve sheath tumor: a rare case in a young patientPaparella Maria Teresa1, Eusebi Laura2 , Mazzucchelli Roberta3, Guglielmi Giuseppe1,41Department of Clinical and Experimental Medicine, Foggia University School of Medicine, Viale L. Pinto 1, 71121 Foggia, Italy; 2Radiology Unit, “Carlo Urbani” Hospital, Jesi, Italy; 3Department of Biomedical Sciences and Public Health, Section of Pathological Anatomy, Polytechnic University of Marche Region, United Hospital, Ancona, Italy; 4Radiology Unit, Barletta University Campus UNIFG, “Dimiccoli” Hospital, ItalyAbstract. Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma that originates from peripheral nerves or from cells associated with the nerve sheath. We report the case of a 30yearold male patient with a history of neurofibromatosis type I (NF-1) and a MPNST located in the lumbar region. The mass was resecated but surgical margins weren’t clear. Recurrence of disease was observed after a few months. A close monitoring of subjects with NF-1 is crucial to diagnose MPNST at an earlier stage and allow a com-plete surgical resection.Key words: malignant peripheral nerve sheath tumors (MPNSTs), soft tissue sarcomas (STS), neurofibroma-tosis type I (NF-1), prognosisIntroductionMalignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas (STS) that origi-nate from peripheral nerves or from cells associated with the nerve sheath, such as Schwann cells or peri-neural cells [1]. MPNSTs account for about 5–10% of STS with an incidence of 0.001% in the general pop-ulation [2], rendering them rare tumors with a poor prognosis [3]. About one half of cases are related to neurofibromatosis type 1 (NF-1) that represents a ma-jor risk for the development of malignancies, particu-larly MPNSTs [4]. This paper presents a rare case of a lumbar MPNST in a 30-year-old male patient with NF-1 from the diagnosis to its clinical course, showing the malignancy of this tumor in terms of a rapid local recurrence and therefore the importance of an early di-agnosis to allow the best therapeutic strategy.Case presentationA 30-year-old male patient presented to our de-partment with a four-month history of paraesthesia and worsening low back pain not responding to nonsteroi-dal anti-inflammatory drugs. There was no history of preceding trauma or accident but the physical exami-nation revealed dark colored spots on the skin (café- au-lait spots) and sporadic subcutaneous nodules refer-ring to his history of NF-1. Laboratory findings, includ-ing leukocyte and platelet counts, hemoglobin, serum creatinine, liver function did not reveal abnormalities. Lumbar spine Magnetic Resonance Imaging (MRI) was performed, revealing a heterogeneous mass of cystic appearance extending medially to the right psoas muscle at L4-L5 level. The lesion showed low signal intensity on T1-weighted images, while high and inhomogene-ous signal on T2-weighted images (Figure 1, A-B).Acta Biomed 2022; Vol. 93, Supplement 1: e20220952In the suspicion of a dermoid cyst, fine-needle aspiration (FNA) biopsies were performed but no his-topathological diagnosis was reached on the basis of the samples obtained. Three months later Computed Tomography (CT) confirmed the presence of a hy-podense mass in lumbar paravertebral region on the right side which pushed anterolaterally psoas muscle, characterized by inhomogeneous enhancement. There was no evidence of associated lymphadenopathy in the scanned area, thus the patient underwent surgery and a subtotal removal of the mass was performed. On gross examination, the tumor measured 6×5 ×3,5 cm and its weight was 100 gr. The cut surface appeared firm and whitish with a translucent area, hemorrhagic and necrotic foci. Microscopically, the tumor was composed by interlacing fascicles of spindle cells with wavy, elongated hyperchromatic nuclei and displayed highly cellular areas alternating with less cellular one (Figure 2, A–C). There was both an increased mitotic index (>10 and <20 per 10 high-power field) and ne-crosis in less than 50% of the tumor (Figure 2, D). Another characteristic of the tumor was some areas with chondrosarcomatous differentiation (Figure 2, E-F). Immunohistochemistry demonstrated posi-tive staining for S-100. Based on these findings, the diagnosis of a MPNST was confirmed. According to the Fédération Nationale des Centres de LutteCon-tre le Cancer (FNCLCC) grading system of STS [5], the tumor was classified as grade 2 (a total score of 5: 2 MPNST, 2 for 10-19/10HPF and 1 for <50% tumor necrosis). Microscopically, the margins showed residual tumor. Radiation therapy was proposed to the patient but he refused it. The postoperative course was initially smooth; lumbar pain disappeared, remaining only a minimal reduction of psoas muscle strength and the following CT examination was negative. Never-theless after one year, the follow-up CT demonstrated a local recurrence of the tumor; a heterogeneous hy-podense mass was found in the right paravertebral side (Figure 3, A-B) at the same level of the excised lesion. The patient received three cycles of systemic chemotherapy with ifosfamide and epirubicin but that was ineffective because the tumor grew up, occupying almost the entire right lumbar region and reaching the inferior border of the liver (Figure 4, A-C).The lesion showed necrotic-colliquative areas and infiltration of both the proximal part of right ureter and right iliac arteries. Moreover, enlarged retroperitoneal lymph nodes were found in the interaortocaval and paraaortic regions. He died two weeks later, fourteen months after the histological diagnosis of MPNST.DiscussionMPNSTs account for 5-10% of all STS, arising in the peripheral nerves and characterizing by a high Figure 1. Lumbar spine MR images show a heterogeneous mass of cystic appearance extending medially to the right psoas muscle at L4-L5 level that is (A) hyperintense on axial T2-weighted image, (B) hypointense on sagittal T1-weighted image.Acta Biomed 2022; Vol. 93, Supplement 1: e2022095 3Figure 2. A)Typical appearance of MPNST with highly cellular areas alternating with less cellular ones (magnification 2X); B) Higher magnification of dense cellular area with spindle cells fascicle and mitotic figure (arrowhaeds) (magnification 20X); C) Higher magnification of hypocellular area with myxoid extracellular matrix (magnification 20X); D) Tumor area with geographic necrosis indicated with asterisk (magnification 20X); E) Tumor area with heterologous mesenchymal differentiation indicated with asterisk (magnification 2X); F) Higher magnification of chondrosarcomatous area (magnification 20X)risk of recurrence and poor outcome [6]. Approxi-mately 50% of cases occur in the context of NF-1, because of the loss of function of NF-1 gene that cod-ifies neurofibromin, an important negative regulator of cellular proliferation [7]; the remaining cases arise sporadically or following radiation therapy [8]. NF-1 has been associated with an increased risk of MPNST, displaying in this association male predominance, young age and infrequent head and neck presentation. Moreover, NF-1 can be considered a negative prog-nostic factor [9] together with large tumor size, truncal location, high grading and a mitotic index of greater Figure 3. Follow-up CT scans demonstrate a heterogeneous hypodense mass in the right paravertebral side; (A): axial unenhanced CT scan, (B): axial enhanced CT scan.Acta Biomed 2022; Vol. 93, Supplement 1: e20220954Figure 4. Last CT scans show an enlargement of the mass which occupies the entire right lumbar region and reaches the inferior border of liver. (A): axial unenhanced CT scan, (B): ax-ial enhanced CT scan shows necrotic-colliquative areas within the mass, (C): coronal enhanced CT scan shows the extention of the lesion till the inferior border of the liver.on T1-weighted images. In our case the tumor shows low intensity on T1-weighted images and high inten-sity on T2-weighted images. The histopathogenesis of MPNST is still unknown but the most important theory is that Schwann cell is the major contributor to the development of both benign and malignant tu-mors of the nerve sheath [2]. This neoplasm rarely can arise from a preexisting benign nerve sheath tumor such as neurofibroma or schwannoma. Microscopi-cally, most tumors are highly cellular and are made of spindle cells with hyperchromatic nuclei and in-distinct cytoplasm. Divergent differentiation can be seen in about 25 % of the tumors and may include osteoid, chondromatous (our case), angiosarcomatou-sand  rhabdomyosarcomatous areas (malignant triton tumor). Nerve sheath differentiation is confirmed by S-100 protein; basing on histological and immuno-histochemical findings, the diagnosis of MPNST can be made. It is generally staged according to the FN-CLCC grading system of STS [13] which is based on 3 factors: differentation, mitotic count and tumor ne-crosis. Each factor is given a score and the results are added to determine the grade of the tumor. The grade of tumor is one of the most important factors which influence patient survival together with the extention of excision. Complete surgical resection with nega-tive (wide) margins is the optimal treatment for this tumor according to standard protocol for managing STS [14], improving the prognosis through decreased rates of local recurrence and distant metastases. Ra-diotherapy can be useful to decrease the incidence of local recurrences [3] but it has not a meaningful role in reduction in both rates of distant metastases and overall survival [15] while chemotherapy has no role in the initial treatment of MPNST for patients without metastases in whom radical resection is ac-complished  [16]. Prognosis of patients with MPNST has always been poor with a 5-year survival rate of 16% to 52% [17].  The 5-year survival rates of pa-tients with MPNST who received surgical resection with and without negative margins have been 67 and 22%, respectively [18]. All this information shows the malignancy and poor outcome that characterize this tumor. Future approaches could involve genomics and proteomics in order to identify molecular biomark-ers as targets for biological therapies [19]; they are not yet well documented for STS, therefore a better than 6/10 high-power fields [10]. MPNST, as STS arising in the abdomen and pelvis, are usually clini-cally silent so that  they can rapidly enlarge until they invade or compress adjacent organs [11]. MRI is the most useful diagnostic tool in the examination of soft tissue malignancies [12]. MPNST usually is hyperin-tense on T2- weighted images and low or isointense Acta Biomed 2022; Vol. 93, Supplement 1: e2022095 59. Evans DG, Baser ME, McGaughran J, et al. Malignant peripheral nerve sheath tumours in neurofibromatosis 1. J Med Genet 2002, 39:311–314.10. Stucky CC, Johnson KN, Gray RJ, et al. Malignant periph-eral nerve sheath tumors (MPNST): the Mayo Clinic expe-rience. Ann Surg Oncol. 2012 Mar;19(3):878-85.11. Levy AD, Manning MA, Al-Refaie WB, Miettinen MM. Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radi-ologic-Pathologic Features, Part 1-Common Sarcomas: From the Radiologic Pathology Archives. Radiographics. 2017 Mar-Apr;37(2):462-483.12. Lisson CS, Lisson CG, Beer M, Schmidt SA. Radiological Diagnosis of Soft Tissue Tumors in Adults: MRI Imaging of Selected Entities Delineating Benign and Malignant Tu-mors. Rofo. 2019 Apr;191(4):323-332. 13. Singh HP, Grover S, Garg B, Sood N. Histopatho-logical Spectrum of Soft-Tissue Tumors with Im-munohistochemistry Correlation and FNCLCC grading: A North Indian Experience. Niger Med J. 2017 Sep-Oct;58(5):149-155.14. Bourcier K, Le Cesne A, Tselikas L, et al.  Basic Knowledge in Soft Tissue Sarcoma. Cardiovasc InterventRadiol. 2019 Sep;42(9):1255-1261. 15. Yang JC, Chang AE, Baker AR et al. Randomized prospec-tive study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol, 16((1)): 197-203, 1998.16. Baehring JM, Betensky RA, Batchelor TT. Malignant pe-ripheral nerve sheath tumor: the clinical spectrum and out-come of treatment. Neurology. 2003 Sep 9;61(5):696-8.17. Baharvahdat H, Ganjeifar B, Roshan NM, Baradaran A. Spinal Intradural Primary Malignant Peripheral Nerve Sheath Tumor with Leptomeningeal Seeding: Case Report and Literature Review. Turk Neurosurg. 2018;28(2):317-322.18. Wong WW, Hirose T, Scheithauer BW, Schild SE and Gunderson LL. Malignant peripheral nerve sheath tumor: Analysis of treatment outcome. Int J Radiat Oncol Biol Phys. 42:351–360. 1998.19. Kobayashi D, Hirayama M, Komohara Y, et al. Translation-ally controlled tumor protein is a novel biological target for neurofibromatosis type 1-associated tumors. J Biol Chem. 2014 Sep 19;289(38):26314-26..Correspondence. Received: October4, 2021Accepted: October 4, 2021Giuseppe Guglielmi, MDProfessor of Radiology, Department of Clinical and Experimental Medicine,Foggia University School of Medicine, Viale L. Pinto 1, 71121 Foggia, ItalyE-mail: giuseppe.guglielmi@unifg.itunderstanding of the cellular and molecular mecha-nisms could in future play an important role in the management of soft tissue masses. In conclusion, in this report we presented a rare case of a young pa-tient with MPNST. It is a malignant sarcoma often associated with NF-1. Histopathology and immuno-histochemistry are fundamental tools to establish the diagnosis. Poor outcome of this tumor is related to its high incidence of local recurrence and distant me-tastases. A complete excision of the lesion represents the best therapeutic strategy to improve the prognosis of the patient. Therefore, a close monitoring of sub-jects with NF-1 and a multidisciplinary approach to management of this lesion is crucial to diagnose MP-NST at an earlier stage and allow a complete surgical resection. Conflict of Interest: Each author declares that he or she has no commercial associations (e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement etc.) that might pose a con-flict of interest in connection with the submitted article.References1. Grobmyer SR, Reith JD, Shahlaee A, Bush CH, Hochwald SN. Malignant Peripheral Nerve Sheath Tumor: molecu-lar pathogenesis and current management considerations. J Surg Oncol. 2008 Mar 15;97(4):340-9. 2. Gupta G, Mammis A, Maniker A. Malignant periph-eral nerve sheath tumors. Neurosurg Clin N Am. 2008 Oct;19(4):533-43.3. Widemann BC. Current status of sporadic and neurofi-bromatosis type 1-associated malignant peripheral nerve sheath tumors. Curr Oncol Rep. 2009 Jul;11(4):322-8. 4. Staedtke V, Bai RY, Blakeley JO. Cancer of the Peripheral Nerve in Neurofibromatosis Type 1. Neurotherapeutics. 2017 Apr;14(2):298-306. 5. American Cancer Society. (2014, December 29). Soft Tis-sue Sarcoma Early Detection, Diagnosis and Staging. https://www.cancer.org/cancer/soft-tissue-sarcoma/detec-tion-diagnosis-staging.html.6. Widemann BC, Italiano A. Biology and Management of Undifferentiated Pleomorphic Sarcoma, Myxofibrosar-coma, and Malignant Peripheral Nerve Sheath Tumors: State of the Art and Perspectives. J Clin Oncol. 2018 Jan 10;36(2):160-167. 7. McPherson JR, Ong CK, Ng CC, et al. Whole-exome se-quencing of breast cancer, malignant peripheral nerve sheath tumor and neurofibroma from a patient with neurofibroma-tosis type 1. Cancer Med. 2015 Dec;4(12):1871-8. 8. Farid M, Demicco EG, Garcia R, et al. Malignant peripheral nerve sheath tumors. Oncologist. 2014 Feb;19(2):193-201. 

Lumbar malignant peripheral nerve sheath tumor: a rare case in a young patient

: Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma that originate from peripheral nerves or from cells associated with the nerve sheath. We report the case of a 30‑year‑old male patient with a history of neurofibromatosis type I (NF-1) and a MPNST located in the lumbar region. The mass was resecated but surgical margins weren't clear. Recurrence of disease was observed after few months. A close monitoring of subjects with NF-1 is crucial to diagnose MPNST at an earlier stage and allow a complete surgical resection

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Lumbar malignant peripheral nerve sheath tumor: a rare case in a young patient

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